Background/Purpose: The eosinophilic granulomatosis with polyangiitis (EGPA) guidelines recommend considering maintenance therapy after remission to reduce the risk of relapse and toxicity, but data on maintenance therapy is limited. The primary objective of this randomized, double-blind trial was to compare rituximab (RTX) and azathioprine (AZA) maintenance therapy on the duration of remission in EPGA patients who had recently achieved vasculitis remission after standard therapy, including tapering/withdrawal of glucocorticoids (GCs).

Methods: Patients with newly diagnosed or relapsing EGPA within 30-360 days of achieving vasculitis remission were randomized to receive maintenance AZA (2 mg/kg/d, 24 months) plus placebo RTX infusions or 500 mg RTX every 6 months for 18 months (4 infusions) plus placebo AZA for 24 months. The primary endpoint was total remission duration over the 28-month study period, defined as the accrued number of weeks a patient remained in remission (BVAS=0) and prednisone ≤7.5 mg/d. Secondary endpoints included the proportion of participants who remained in remission (i) with prednisone ≤7.5 mg/d during the 28-month study period; (ii) regardless of GC dose; (iii) with prednisone ≤4 mg/d at month 18 and month 28; percentage of patients with ≥1 vasculitis flare; of those with ≥1 clinically significant asthma/rhinosinusitis exacerbations; cumulative GC dose; adverse events; damage, disability and quality of life.

Results: 98 patients were enrolled from 36 centers between March 2018 and June 2022, 49 per arm: newly diagnosed (75%), MPO-ANCA+ (49%), five-factor score (FFS) ≥1 (46%), remission achieved with GCs only (29%). The mean number of weeks in remission with prednisone ≤7.5 mg/d was 96.0 vs 91.1 in the AZA and RTX arms, respectively (mean difference 5.0; 95% CI [-6.2 to 16.1]). The percentage of patients who remained in remission during the 28-month study period (i) with prednisone ≤7.5 mg/d was 11/49 (22.5%) vs 17/49 (34.7%) (RR 0.66 [0.37 to 1.20]) and (ii) regardless of GC dose was 31/49 (63.3%) vs 41/49 (83.7%) (RR 0.76 [0.60 to 0.94]) in the AZA and RTX arms, respectively. The percentage of patients in remission with prednisone ≤4 mg/d was (i) 25/49 (51.0%) vs 34/49 (69.4%) at month 18 (RR 0.79 [0.60 to 1.02]) and (ii) 23/49 (46.9%) vs 37/49 (75.5%) at month 28 (RR 0.62 [0.48 to 0.80]) in the AZA and RTX arms, respectively. The relapse rate for vasculitis was 22.2% vs 14.4%, and the rate of clinically significant exacerbations of asthma and/or rhinosinusitis was 40.5% vs 32.7% in the AZA vs RTX arms, respectively. No differences were found in the cumulative GC, damage, disability, or quality of life. One patient in the AZA group died of SARS-CoV2 infection before the vaccine was developed. No difference in serious adverse events was observed.

Conclusion: Following remission within the previous year after a new EGPA diagnosis or vasculitis relapse, RTX did not show overall superiority to AZA in maintaining vasculitis remission, reducing asthma/rhinosinusitis exacerbations or sparing GC. However, RTX was superior to AZA in maintaining remission with prednisone ≤4 mg/d at month 28. It remains to be determined whether RTX can reduce vasculitis relapse rates in ANCA-positive patients, who are at a higher risk of relapse.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/maintenance-of-remission-with-rituximab-versus-azathioprine-in-newly-diagnosed-or-relapsing-eosinophilic-granulomatosis-with-polyangiitis-a-prospective-randomized-controlled-double-blind-trial/